Project Summary/Abstract Patients with Anorexia Nervosa (AN) can become medically unstable due to malnutrition and require hospitalization for re-feeding, or nutritional repletion. The goal of re-feeding is weight gain, since weight gain in hospital is a key predictor of long-term recovery. However, extreme caution has been used during re-feeding since the re-feeding syndrome was first described in the 1950's. This syndrome is caused by rapid shifts in fluids and electrolytes in response to nutrients and can result in cardiac failure, delirium and death. Since it was documented in patients with AN, conservative consensus-based recommendations were developed and have been applied broadly to ensure safety during re-feeding. These recommendations call for starting around 1200 calories per day and advancing slowly by 200 calories every other day. We recently demonstrated this start low and go slow approach contributes to poor weight gain and prolonged hospital stay in adolescents with AN. These findings have contributed to recognition of the underfeeding syndrome, characterized by prolonged illness and even death due to overly cautious re-feeding. In a follow-up study, we found double the weight gain on 1800 vs. 1200 calorie diets with no increase in risk. While these short-term results look promising, the long- term impact is unknown. Overall Objective: The purpose of the proposed longitudinal observational study is to compare long-term recovery in adolescents with AN re-fed on higher vs. lower calories in hospital. Our Study of Adolescents Hospitalized with Anorexia Nervosa (SHAAN) has enrolled 56 adolescents to date. This is the largest cohort of participants re-fed on higher vs. lower calorie protocols and prospectively followed in a Pediatric Clinical Research Center. We are now proposing to examine their recovery retrospectively for one- year after discharge from hospital. These findings will be used as preliminary data to plan a large multicenter trial comparing re-feeding approaches. Specific Aims: We will compare weight and vital sign recovery, return of menses and rates of rehospitalization over one year following discharge from hospital in adolescents re-fed on higher vs. lower calories. Our overarching hypothesis is that higher calories and faster weight gain will lead to earlier physical and nutritional recovery and less frequent rehospitalization. Study Design: This retrospective chart review will extract existing data from the medical records in our outpatient clinic, where we provided follow-up care to the SHAAN cohort. We will compare recovery trajectories between subjects re-fed on higher vs. lower calories during hospitalization and at 8 time points following hospitalization: wks. 1, 2, 3, 4, and mo. 3, 6, 9, 12. Significance: Balancing risk for the re-feeding syndrome with the need for weight gain in hospitalized patients with AN represents a fundamental paradox for clinical practice. While the current recommendations for lower calorie diets appear to minimize risk, they also contribute to the underfeeding syndrome. Long-term follow-up data are required to determine the impact of higher calorie re-feeding. The proposed study is an essential next step to building evidence-based approaches to re-feeding in AN.